Respiration induced tumor motion causes both artifacts on computed tomography images and leads to inaccuracies in the planning and delivery of radiation therapy treatments. Conventional solutions included adding a "safety margin" around the tumor which can often result in unnecessary irradiation of normal tissue thereby increasing normal tissue toxicity. Current commercially available methods with linear accelerators include breath-holds and gating during radiation delivery. The former is not tolerated well by patients while the later increases treatment delivery time, thereby increasing the risk of spurious patient motion and even reducing the biological effectiveness of the delivered radiation. The goal of this proposal is to develop a real- time motion-synchronized treatment couch using feedback control. The specific aims of this proposal are to 1) design and test the feasibility of a prototype respiration induced motion-synchronized treatment couch for RT delivery and 2) develop an inferential model using skin markers that will correlate their position with tumor motion using partial-least squares (PLS) models. In order to develop this treatment couch, the couch dynamics and control system will be modeled and tested on patient-specific tumor motion trajectories. Once the development of the prototype controller and couch has been completed, a full system test will be performed. Inferential models using partial least squares regression will be developed to predict the position of the tumor using motion surrogates placed on the skin of the patient. Its robustness will be tested with respiration data acquired on multiple treatment days. The results from our proposal have the potential to significantly impact radiation therapy of lung and upper abdominal cancers. The proposed exploratory research effort will provide the foundation for further development of a real-time motion management framework using a real-time motion-synchronized treatment couch. Its eventual implementation in clinical practice will lead to reduced normal tissue toxicity through the use of smaller tumor margins and accurate tumor tracking. This will enable more widespread use of highly conformal treatments such as intensity- modulated radiation therapy (IMRT) and stereotactic body radiation therapy (SBRT) (which are highly unforgiving of tumor motion) in a reliable manner. [unreadable] [unreadable] [unreadable]